Epidemiologic insights on the role of fibroblast growth factor 23 in cardiovascular disease

Fibroblast growth factor 23 (FGF23) regulates phosphate and vitamin D homeostasis and rises as kidney function declines. Animal studies have demonstrated direct and indirect effects of FGF23 that may promote heart disease. Herein, we review the recent epidemiologic literature evaluating the relationship between FGF23 and cardiovascular disease.

In observational prospective studies, higher FGF23 associates with a greater risk of incident cardiovascular disease including ischemic heart disease, stroke, heart failure, and atrial fibrillation. These studies establish a temporal sequence of events over long-term follow-up that suggest a possible role of FGF23 in cardiovascular disease pathogenesis. In most studies, risk is generally graded; however, in the largest study to date, higher FGF23 within the low-normal range was not associated with higher risk. In several recent studies higher FGF23 associated more strongly with the risk of congestive heart failure compared with atherosclerotic events, a finding consistent with surrogate endpoints and animal experiments. Currently, the utility of FGF23 as a predictive biomarker of cardiovascular risk is not established, and interventions to reduce FGF23 need to be studied to confirm its possible pathophysiologic role.

Higher FGF23 is associated with the subsequent development of cardiovascular disease, and perhaps most notably heart failure, in a growing number of studies. These findings bolster ongoing efforts to lower FGF23 using strategies to reduce phosphate intake and absorption.